免疫细胞介导的血浆代谢物与膝骨关节炎的因果关系:孟德尔随机化研究  

Immune cell-mediated causal relationship between plasma metabolites and knee osteoarthritis:a Mendelian randomization study

作　　者：王振宇 张洪美[1] 荆琳[1] 闫奇[1] 汤吉祥 葛骐瑞 WANG Zhenyu;ZHANG Hongmei;JING Lin;YAN Qi;TANG Jixiang;GE Qirui(Wangjing Hospital of China Academy of Chinese Medical Sciences,Beijing 100102,China;Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]中国中医科学院望京医院,北京100102 [2]宁夏医科大学,银川750004

出　　处：《军事医学》2024年第10期778-785,共8页Military Medical Sciences

基　　金：北京市科委科技计划项目(Z20110005520058);中国中医科学院科技创新工程项目(CI2021A02005)。

摘　　要：目的采用孟德尔随机化(MR)系统评价血浆代谢物与膝骨关节炎(KOA)风险之间的因果关系及免疫细胞的潜在中介或遮掩效应。方法通过全基因组关联分析(GWAS)数据库获取1400种血浆代谢物、731个免疫细胞特征和KOA的GWAS数据,采用双向MR分析对血浆代谢与KOA的因果关系进行系统评价,并通过两步法中介MR分析评估可能具有中介或遮掩效应的免疫细胞特征。结果双向MR分析结果经敏感性分析筛选后,共发现65种血浆代谢物、35个免疫细胞特征与KOA存在因果关系(P<0.05)。中介分析发现,相对细胞计数CD45RA^(+)CD28^(-)CD8br Treg与CD8br Treg之比(CD45RA^(+)CD28^(-)CD8br%CD8br)在3种代谢物(水杨酸、X-07765、X-23739)与KOA风险的因果关系中存在中介效应,其中水杨酸为遮掩效应,效应比0.0412。结论多种血浆代谢物及免疫细胞特征与KOA存在因果关系,KOA不应视为单纯的退行性关节病。其中水杨酸对KOA的保护作用可能因其诱导Treg细胞的分化作用而受到削弱,值得进一步研究。Objective To evaluate both the causal relationship between plasma metabolites and the risk of knee osteoarthritis(KOA)and the potential mediating or masking effect of immune cells using Mendelian randomization(MR)systems.Methods The GWAS data on 1400 plasma metabolites,731 immune cell traits and KOA was retrieved from the genome-wide association study(GWAS)database.Two-way MR analysis was used to evaluate the causal relationship between plasma metabolism and KOA.Two-step mediation MR analysis was conducted to evaluate immune cell traits that might have mediating or masking effects.Results After sensitivity analysis and screening,65 plasma metabolites and 35 immune cell traits were found to have causal relationships with KOA(P<0.05).Mediation analysis found that CD45RA^(+)CD28^(-)CD8br%CD8br had a mediating effect in the causal relationship between three metabolites(2-hydroxyhippurate,X-07765,X-23739)and the risk of KOA.2-hydroxyhippurate(salicylic acid)exerted a masking effect,and the effect ratio was 0.0412.Conclusion A variety of plasma metabolites and immune cell traits are causally related to KOA,which should not be regarded as a simple degenerative joint disease.The protective effect of salicylic acid against KOA may be weakened by its role in inducing the differentiation of Treg cells,which is worthy of more studies.

关 键 词：膝骨关节炎 血浆代谢物 免疫特征 因果关系 孟德尔随机化 中介分析 

分 类 号：R684.3[医药卫生—骨科学]